Cognitive enhancement interventions are effective for schizophrenia: why not provide them early?
Authors: Matcheri S. Keshavan, Shaun M. Eack
Journal: World Psychiatry (2023)

There has been considerable optimism in the care of early course psychotic disorders in recent years, as reflected by the rapid implementation of coordinated specialty care (CSC) services around the world in the background of steadily progressing standards of care. While benefits are seen early with CSC interventions, these results may not be sustained. In a large 10-year follow-up study (N=347), it was found that the early intervention group had less overall utilization of psychiatric bed days (suggesting less psychosis). However, there were few differences from the treatment-as-usual group in regard to improving long-term functional outcomes such as those related to independent living, relationships or work1. There is clearly a need to examine the critical elements of care that would improve long-term outcomes in early course psychosis2. Cognitive impairments are a core feature of schizophrenia and related psychotic disorders. They are present in a large majority of patients, tend to persist before, during and after psychotic episodes, and robustly predict outcomes. They are also strongly related to the underlying neurobiology and the genetic underpinnings of the illness. There is robust evidence that cognitive enhancement treatments are effective in ameliorating cognitive deficits as well as improving functional ability in schizophrenia. Improvements are stronger when they are integrated in a coordinated care model including other psychosocial rehabilitation approaches, and when efforts are made to facilitate the transfer of cognitive gains to the real world3. An emerging but small body of literature, including our own studies4, points to the importance of cognitive enhancement in the early course of psychotic disorders. First, findings to date indicate that such interventions can promote important functional gains in critical recovery domains, including employment and social functioning, in early psychosis. While a recent meta-analysis found that cognitive enhancement intervention effects appear largely consistent across durations of illness3, other studies have found benefits, including generalization to community functioning, to be greater when using an early intervention strategy5. Second, deficits in cognition lead to incremental costs related to unemployment, poor quality of life and loss of independence6. There are unique windows of opportunity for functional gains during the early course of illness, before the entrenchment in a disability can take hold. Third, the early phases of psychosis are associated with greater brain “reserve”, which promotes response to cognitive enhancement. This is supported by evidence that higher grey matter volumes at baseline are associated with larger early improvements with cognitive training7. This may reflect greater brain plasticity early in the illness and provides an impetus for the application of such intervention as early as possible. Fourth, there is evidence of progressive cognitive decline and grey and white matter loss over the course of the illness at least in a subgroup of patients with schizophrenia8. Cognitive enhancement approaches have been shown to be associated with less grey matter loss over time and may therefore be neuroprotective, or may at least slow the progression of cognitive and brain function. Finally, evidence continues to point to cognitive impairment as a key rate-limiting factor for improved outcomes from a variety of CSC components, most notably supported employment. The goals of cognitive enhancement are synergistic with those of CSC, with both emphasizing reduction of disability. Cognitive enhancement interventions are generally considered recovery-phase approaches, whereas the earliest components of CSC, such as individualized medication and family psychoeducation, must necessarily focus on stabilization. Such stability is likely critical for engagement in psychosocial interventions and, once attained, cognitive enhancement interventions could support subsequent CSC recovery goals of employment, social integration, and independence. If cognitive impairments begin early, and cognitive enhancement interventions are generally effective across phases of psychosis, why are they not widely implemented? Current CSC models applied throughout the world have done much to advance psychosocial treatments to improve early course outcomes, but few of these programs offer the opportunity for patients to participate in cognitive enhancement interventions. In our recent review, none of the 13 published CSC programs included cognitive enhancement2. Challenges associated with the implementation of a novel psychosocial treatment in already resource-limited community practice settings (e.g., cost, low fidelity of implementation, lack of trained personnel, and higher prioritization for addressing more acute symptoms) are likely contributing factors limiting the availability of cognitive enhancement interventions for early course patients. How do we go about integrating cognitive enhancement interventions in CSC settings? These interventions target broad neurocognitive impairments in attention, memory and problem-solving, and challenges in social cognition, such as difficulties in taking the perspective of others and accurately appraising the social context. Schizophrenia and related conditions are highly heterogeneous, even in the early course. As such, specific targets will vary across individuals. Brief assessments of cognition that are more clinician friendly, such as the Brief Assessment of Cognition in Schizophrenia (BACS) and the National Institutes of Health Toolbox Cognition Battery (NIH Toolbox CB), can be used early in CSC settings to help identify the subjects in whom cognitive enhancement interventions are indicated and to personalize such interventions. Evidence is also emerging about the beneficial effects of cognitive enhancing interventions on negative symptoms9, a domain that is largely untreated in psychosis but contributes to substantial functional disability. Further, cognitive enhancement approaches show potential for reducing some common substance use problems, and meta-cognitive interventions hold promise for promoting treatment adherence and greater insight into the condition. In addition, through participation in cognitive enhancement interventions, patients in CSC could have greater ability to engage in more frequently implemented components of the CSC programs (such as family education, supportive employment/education, social skills training and individualized psychotherapy and psychopharmacology)2. Fundamentally, the field needs to address several gaps in the way we understand and treat core aspects of schizophrenia. Despite the growing evidence outlined above, cognitive deficits are still not part of the diagnostic criteria for schizophrenia. Including them in future revisions of our diagnostic systems will serve to promote routine cognitive testing as part of baseline assessments. There is evidence that individuals with more severe illness, and those with baseline cognitive and functional impairments, may be optimal candidates for cognitive enhancement interventions3. Baseline cognitive and functional assessments are therefore likely to help identify patients most in need for cognitive enhancement interventions. We need to know whether a stratified intervention approach early in the illness may be a cost-effective strategy. Finally, there is preliminary evidence that cognitive enhancement approaches are effective in individuals at high clinical risk for psychosis, though more work is needed to confirm these observations and identify potential characteristics of who might best respond. Introducing cognitive enhancement interventions early in the course of psychoses following symptom stabilization, in the context of the synergistic effects of an integrated, multi-element model of care, represents the next generation of early interventions for psychosis and holds promise for favorably modifying the long-term course of the illness.